A patient with acute myelomonocytic leukemia (M4 in FAB classification) refractory to various kinds of intensive chemotherapy was intravenously administered low doses (7 or 14 mg/m2) of aclacinomycin-A (ACM-A) daily. This increased mature neutrophils and monocytes and decreased leukemia cells in the peripheral blood. Pelger Huet-like nuclear anomaly, observed in the neutrophils, suggested the leukemic nature of these cells. The in vivo findings were clearly correlated with the in vitro results in which ACM-A could induce myelomonocytic differentiation of the leukemia cells. During the course of the treatment, the patient achieved and maintained good general condition for more than nine months after the initiation of the treatment. In clinical trials, nine patients, five with acute myeloid leukemia (AML) and four with myelodysplastic syndrome (MDS), were treated with low doses of ACM-A. Five patients, three AML and two MDS, responded to the treatment. The results suggest that low doses of ACM-A may induce in vivo differentiation of leukemia cells, and may be a potential therapeutic strategy in the treatment of AML or MDS that is refractory to conventional chemotherapy.